Meta-analysis of single strain probiotics for the eradication of Helicobacter pylori and prevention of adverse events

AIM: To assess the efficacy and safety of single strain probiotics for the: (1) eradication of Helicobacter pylori (H. pylori); (2) prevention of adverse events; and (3) prevention of antibiotic-associated diarrhea associated with eradication therapy. METHODS: We searched PubMed (1960-2014), EMBASE (1974-2014), Cochrane Database of Systematic Reviews (1990-2014), and ISI Web of Science (2000-2014). Additionally, we conducted a grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroenterology meetings, experts in the field and correspondence with authors. Randomized controlled trials of H. pylori positive adults or children treated with eradication therapy and assessing the adjunctive therapy with a single strain of probiotics were included. The primary outcomes were the rates of eradication of H. pylori and frequency of patients with adverse events or antibiotic-associated diarrhea. Outcomes were pooled using fixed or random-effects models to calculate the relative risk and corresponding 95%CI and weighted on study size. To explore possible explanations for heterogeneity, a priori subgroup analyses were conducted on daily probiotic dose, study population, and quality of the study. The overall quality of the evidence for each probiotic strain was assessed using the GRADE criteria. RESULTS: A total of 25 randomized controlled trials (28 treatment arms, with a total of 3769 participants) assessed one of six single probiotic strains as adjunctive treatments to standard eradication therapy. Only one probiotic strain significantly improved H. pylori eradication rates: Saccharomyces boulardii (S. boulardii) CNCM I-745 [pooled relative risks (pRR) = 1.11, 95% CI: 1.07-1.16]. Only one probiotic strain (S. boulardii CNCM I-745) significantly prevented any adverse events (pRR = 0.42, 95% CI: 0.28-0.62). Both S. boulardii CNCM I-745 and Lactobacillus rhamnosus GG significantly reduced antibiotic-associated diarrhea (pRR = 0.47, 95%CI: 0.37-0.60 and pRR = 0.29, 95%CI: 0.17-0.48, respectively) associated with H. pylori eradication therapy. Meta-regression of sub-groups did not detect significant differences by dose, adult vs pediatric, symptom status, or study quality, but did find significant differences by the strain of probiotic. Potential mild publication bias was found for antibiotic-associated diarrhea, but not for eradication or adverse event outcomes. Analysis of the study quality illuminated areas for improvement in future studies (use of placebos, study size calculations, attrition reasons and discussion of limitations and generalizability). CONCLUSION: The pooled evidence suggests that the adjunctive use of a few probiotic strains may improve H. pylori eradication rates and prevent the development of adverse events and antibiotic-associated diarrhea in those treated with standard eradication therapies. The type of probiotic strain was the most important factor in predicting efficacy.